Volume reduction surgery (VRS) has recently been successfully employed for the treatment of end stage chronic obstructive pulmonary disease (COPD). Improvement in lung function following VRS is thought to be directly related to resection of emphysematous lung tissue which, to date, has been accomplished using several distinct, but equally successful, surgical approaches. Independent of the technique employed, the therapeutic objectives of the VRS are the same: to eliminate target regions with diseased and dysfunctional lung tissue, and to produce overall reduction in lung hyper-expansion with the objective of improving elastic recoil, airway tethering, and respiratory muscle function. Given this objective, we hypothesize that effective, controlled, and clinically safe volume reduction can be achieved bronchoscopically using a non-surgical approach which can reduce the volume of selected target regions without requiring section of lung tissue. The rationale for this hypothesis is based on a consideration of the surface tension and tissue recoil forces which dictate alveolar stability, and how the balance between these factors can be altered. By using biocompatible solutions capable of altering this force balance which are installed into selected target regions using a bronchoscope, it should be possible to generate directed, sustained alveolar collapse into selected target regions using a bronchoscope, it should be possible to generate directed, sustained alveolar collapse, and thus, in effect, achieve lung volume reduction. Preliminary studies suggest that 3 steps will be required. The initial intervention involves instillation of biocompatible solutions ("anti-surfactants") which increase surface tension at the air-liquid interface of small airways and alveoli, resulting in force imbalance and collapse. Two strategies are being considered to ensure that any gas trapped within the target region can be effectively eliminated to allow for approximation of adjacent alveolar surfaces. These interventions are accomplished by specific maneuvers to promote fibroblast in growth and permanent scarring. The final result should be sustained volume reduction, functionally equivalent to that which can be achieved surgically. If this hypothesis is correct, the methodology proposed here has the potential for reducing morbidity and mortality associated with volume reduction surgery, and for making the procedure available to patients with end stage lung disease who might not otherwise be eligible for surgery because of the presence of significant co-morbidity. The objective of this proposal is to test this hypothesis, and develop bronchoscopic volume reduction to such an extent that it could be considered for human trials.